Linked Life Data

17086192

Source:http://linkedlifedata.com/resource/pubmed/id/17086192

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7123
pubmed:dateCreated
2007-1-4
pubmed:databankReference
pubmed:abstractText
Protein phosphatase 2A (PP2A) is a principal Ser/Thr phosphatase, the deregulation of which is associated with multiple human cancers, Alzheimer's disease and increased susceptibility to pathogen infections. How PP2A is structurally organized and functionally regulated remains unclear. Here we report the crystal structure of an AB'C heterotrimeric PP2A holoenzyme. The structure reveals that the HEAT repeats of the scaffold A subunit form a horseshoe-shaped fold, holding the catalytic C and regulatory B' subunits together on the same side. The regulatory B' subunit forms pseudo-HEAT repeats and interacts with the C subunit near the active site, thereby defining substrate specificity. The methylated carboxy-terminal tail of the C subunit interacts with a highly negatively charged region at the interface between A and B' subunits, suggesting that the C-terminal carboxyl methylation of the C subunit promotes B' subunit recruitment by neutralizing charge repulsion. Together, our structural results establish a crucial foundation for understanding PP2A assembly, substrate recruitment and regulation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1476-4687
pubmed:author
pubmed:issnType
Electronic
pubmed:day
4
pubmed:volume
445
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
53-7
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Crystal structure of a protein phosphatase 2A heterotrimeric holoenzyme.
pubmed:affiliation
Department of Biological Structure, University of Washington, Seattle, Washington 98195, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't